The long term objective is to clarify the mode of action of water-soluble forms of vitamin A in stimulating cellular differentiation and in showing beneficial therapeutic effects on skin without toxicity. The specific aims are: 1) To synthesize new water-soluble derivatives of retinoic acid that show promise of possessing valuable biological or therapeutic effects, 2) To study the metabolism of these compounds in vivo and in isolated tissue cells in vitro, 3) To clarify the mechanisms of their actions in cellular differentiation, and 4) To probe the mechanisms underlying the teratogenicity of some water- soluble forms and the nonteratogenicity of others. The planned studies are directly relevant to the use of retinoids as therapeutic agents in skin disorders and neoplasm and to an understanding of teratogenicity and retinoid toxicity.